Project Summary Corneal melting is the uncontrolled, excessive degradation of cellular and extracellular components of the cornea, and occurs mainly to patients with bacterial or viral corneal infections, autoimmune diseases, chemical burns, and those who undergo various ocular surgical procedures. This is a potential cause of corneal blindness and has no satisfying cure currently. The most recent understanding is that an overexpression of various matrix metalloproteinases (MMPs) catalyzes the cleavage of collagen and is the main culprit of corneal melting. MMPs are zinc-dependent enzymes and their overexpression is indicated in numerous other pathological states including metastatic cancers. A common approach to treat abnormally high MMP activities is the use of MMP inhibitors (MMPi), which deactivate MMPs by binding the zinc-containing catalytic domain through the zinc binding group (ZBG). However, most MMPi are associated with serious side effects, such as musculoskeletal immobility, once they enter the body?s circulation and lack of specificity. The application of MMPi for corneal melting is no exception. The objective of the current proposal is to incorporate dipicolylamine (DPA), which has a high affinity and selectivity towards zinc ions, into a widely used poly(2-hydroxyethyl methacrylate) (pHEMA)-based contact lens. The central hypothesis of this proposal is that DPA-containing pHEMA (pDPA-HEMA) hydrogels will absorb a significant amount of zinc ions from the cornea, resulting in decreased MMP activities and thereby reducing corneal melting significantly. Our preliminary data clearly demonstrate the feasibility of this approach. The specific aims of this research are (1) to measure MMP activity in the presence of DPA-containing HEMA (pDPA-HEMA) hydrogel and (2) to demonstrate in vitro biocompatibility of pDPA-HEMA hydrogel. The completion of the first aim will provide us with the design principles to modulate the physical and chemical properties of the hydrogels, and enable us to find the optimally functional composition of pDPA-HEMA for treating corneal melting. The completion of the second aim will confirm the biocompatibility and minimized side effects of this novel approach in treating corneal melting. Corneal melting is a debilitating ocular symptom which threatens vision for many. We believe that this proposed research will contribute significantly in advancing the treatment for this important ocular disorder.